The comorbidity of alcohol dependence with major psychiatric illness, including affective disorders, is receiving increased attention in the psychiatric literature. However, little systematic research has been done on patients with primary depression and secondary alcoholism. These patients, who typically claim to "self-medicate" their depression with alcohol, are interesting to study because their choice of psychoactive substance may provide a clue to the neurochemistry underlying their symptoms. During this period, we completed a pilot study comparing patients with a history of comorbid primary depression and secondary alcohol dependence to two comparison groups: patients with a history of depression but no history of alcohol abuse or dependence, and patients with a history of alcohol dependence but no affective illness. Patients were matched according to age, sex, and Global Assessment of Functioning score. Eleven patients in each group completed a standardized work-up in which we characterized symptoms, family history, and pattern of drug and alcohol abuse. Results indicate that comorbid patients are significantly more likely than depressed patients to meet DSM-III-R criteria for panic disorder (p=0.04). Compared to depressed patients, comorbid patients have significantly higher hypomania scores (p=0.03) although (with the exception of one comorbid patient) neither the depressed nor the comorbid patients met criteria for bipolar illness. In particular, comorbid patients with primary depression and secondary alcoholism may tend to be "trimorbid", with symptoms of depression, anxiety, and alcoholism. Furthermore, the increased anxiety and irritability experienced by the comorbid patients may contribute to their tendency to abuse alcohol. In conjunction with the above project, we developed a questionnaire to study patients' use of alcohol, carbohydrates, and caffeine in response to specific depressive symptoms. The questionnaire has been administered to patients with seasonal affective disorder, nonseasonal affective disorder, primary depression with secondary alcohol dependence, alcohol dependence without affective disorder, and normals. The data is currently being analyzed to establish test-retest reliability, and to ascertain differences between the groups in their use of these substances.